Methods are being devised and tested to improve the detectability of trace organic compounds using mass spectrometry. The development of new derivatization reagents and methods to impart improved electron capture properties and ionizability for negative ionization mass spectrometric detection has been continued and applied to the analysis of GABA in brain tissue. Improved injection techniques have been applied to tissue analyses of kynurenine by GC/MS. Liquid-chromatography - electrospray mass spectrometry methods continue to be developed for trace detection of oxidized nucleosides and the quantitative analyses of 13C-labelled NAD and NADP as products of 13C- tryptophan metabolism. The coupling of capillary zone electrophoresis and electrospray mass spectrometry is being pursued to enable enhanced detection of peptides and mixtures isolated from cell extracts and tissues.